SURGICAL TREATMENT OF MODERATE ISCHEMIC MITRAL REGURGITATION THE

SURGICAL TREATMENT OF MODERATE ISCHEMIC MITRAL REGURGITATION: THE CARDIOTHORACIC SURGICAL TRIALS NETWORK Robert E. Michler, M. D. For the CTSN Investigators AHA Late Breaking Clinical Trials November 18, 2014

The Many Faces of MR • Primary MR • Structural (degenerative) valve and sub-valvular disease • Secondary MR • Functional Impairment of the LV • Ischemic • Non-Ischemic

Epidemiology of Ischemic MR • 50% of MI’s are associated with some degree of ischemic MR • 10% of MI’s are associated with moderate ischemic MR • Ischemic MR is associated with reduced event-free survival AHA Heart and Stroke Facts 2014

Surgical Treatment Options Considerations: CABG alone: improves LV function and MR CABG + MVr: persistent adverse consequences of MR

2014 AHA/ACC Guidelines Chronic Moderate Secondary MR Recommendations MV repair may be considered for patients with chronic moderate secondary MR (stage B) who are undergoing other cardiac surgery COR LOE IIb J Am Coll Cardiol. 2014; 63(22): e 57 -e 185. doi: 10. 1016/j. jacc. 2014. 02. 536 C

CTSN Moderate MR Trial Design Patients Screened for Moderate Ischemic MR (n=6, 676) Randomized Patients (n=301) CABG Alone (n=151) CABG + Valve Repair Undersized Ring (n=150) Outcomes Measured at 6, 12 and 24 months Primary Endpoint Analysis (n=301)

Primary Endpoint • Degree of left ventricular reverse remodeling as measured by changes in LVESVI • Powered (90%) to detect a decrease in LVESVI of 12 m. L/m 2 with repair compared to CABG alone at 12 months

Secondary Endpoints • MACCE • Mortality • Residual MR • Serious adverse events • Hospitalizations • Quality of life

Integrative Method of MR Grading (ASE Guidelines: Zoghbi W. et al. JASE 2003; 16: 777 -802) Parameter Mild Moderate Severe EROA(cm 2) <0. 2 - 0. 39 ≥ 0. 4 VC width (mm) <3 3 - 6. 9 ≥ 7 Jet/LA area <20% 20 -39% ≥ 40% EROA Vena Contracta Jet area/LA Ratio

Baseline Characteristics Male –no. (%) CABG Alone (N=151) 99 (65. 6) CABG + Repair (N=150) 106 (70. 7) Age (yr) 65. 2 ± 11. 3 64. 3 ± 9. 6 White –no. (%) 122 (80. 8) 115 (76. 7) Hispanic–no. (%) 14 (9. 3) 12 (8. 0) Diabetes –no. (%) 66 (43. 7) 76 (50. 7) 28 (18. 7) 24 (16. 0) 4 (2. 8) Prior PCI 24 (15. 9) 26 (17. 3) Heart Failure 76 (50. 3) 82 (54. 7) Myocardial Infarction 97 (64. 2) 103 (68. 7) Atrial Fibrillation 35 (23. 3) 19 (12. 8) ICD 6 (4. 0) Stroke 9 (6. 0) 15 (10. 0) Medical and Surgical History –no. (%) Renal Insufficiency Prior CABG

Change in LVESVI at 1 Year Median with 95% CI for change in LVESVI (1 Year – baseline) Change in LVESVI (m. L/m 2) Z=0. 50, p=0. 61 (All patients) CABG Alone CABG + MV Repair (All Patients) CABG Alone CABG + MV Repair (Survivors)

Mortality 30 Day Mortality: 2. 7% (CABG) vs. 1. 3% (CABG/MVr), p =0. 68 12 Month Mortality: 7. 3% (CABG) vs. 6. 7% (CABG/MVr), p =0. 83

MACCE at 12 Months

Operative Conduct and Length of Stay CABG Alone CABG + MV Repair P-value 3. 3± 0. 9 3. 2± 0. 9 NS Aortic XClamp (min) 74. 7± 36. 7 117. 2± 35. 4 <0. 001 CPB time (min) 106. 8± 49. 7 163. 1± 54. 9 <0. 001 ICU stay 4. 0± 5. 7 4. 8± 6. 1 0. 006 Postoperative LOS 9. 4± 5. 9 11. 3± 8. 2 0. 002 No. of Grafts Data presented as mean±std

Rates of Serious Adverse Events and Re-hospitalization Overall SAE Rate (100 -pt years) 117. 0 (CABG Alone) vs. 137. 1 (CABG + Repair) p=0. 15 P=NS

Mitral Regurgitation

Quality of Life at 1 year

NYHA Classification & Death

Unique Features • MR was consistently measured using an integrative method in an echo core lab • Trial represents a study population with Moderate Ischemic MR • 30 day and 1 year mortality excellent

Limitations • Primary end point not a clinical endpoint • Trial with mortality endpoint would require several thousand patients and multiple years of follow up • Only 1 year results reported • 2 year follow up pending

Summary • No difference at 1 year: • in the degree of reverse remodeling • in mortality • in MACCE, hospital readmission, or QOL • CABG + MV repair associated with more: • neurologic events • increased cross clamp and cardiopulmonary bypass time • longer ICU and hospital LOS • At 1 year, higher degree of moderate and severe MR in the CABG alone group

Conclusion • The trial did not demonstrate a clinically meaningful advantage to the routine addition of MVr to CABG • Longer-term follow-up is ongoing • Will the lower incidence of moderate or severe MR at one-year translate into a net clinical benefit for patients undergoing CABG + mitral repair?

MMR Investigators • • • • Data Coordinating Center: In. CHOIR Montefiore – Einstein Emory University Duke University Hôpital Laval University of Virginia Health System Montreal Heart Institute University of Pennsylvania Columbia University Medical Center Cleveland Clinic Foundation University of Maryland Brigham and Women's Hospital Sacré-Cœur de Montréal Ohio State University Medical Center • • • • East Carolina Heart Institute Wellstar / Kennestone Baylor Research Institute University of Southern California St. Michael’s Hospital Toronto General Hospital Mission Hospital NIH Heart Center at Suburban Hospital Inova Heart & Vascular Institute University of Alberta Hospital Centre Hospitalier de l'Université de Montréal Sunnybrook Health Sciences Centre Aarhus University

Acknowledgements • Supported by U 01 HL 088942 Cardiothoracic Surgical Trials Network (CTSN) • Funding Agencies: • National Heart, Lung, and Blood Institute • National Institute of Neurological Disorders and Stroke • Canadian Institutes for Health Research

Distribution of Ring Size 1 2

LVESVI Distribution at Baseline

History of MI and LVESVI Change

MR at 1 Year and LVESVI Change